Renin-angiotensin activating system

From Dog

The renin-angiotensin-aldosterone system (RAAS) is a collection of integrated hormones critical in maintaining the volume of extracellular fluid, blood pressure, and electrolyte homeostasis[1].

RAAS hormones are regulated as part of the normal renal physiology and cardiac functions and thus are affected by diseases such as chronic renal disease or congestive heart failure.

A decrease in blood pressure results in a decreased concentration of sodium and chloride ions at the macula densa within the renal cortex. In the kidney, the macula densa is an area of closely packed specialized cells lining the wall of the distal convoluted tubule (DCT) at the point of return of the nephron to the vascular pole of its parent glomerulus glomerular vascular pole[2].

The cells of the macula densa are sensitive to the ionic content and water volume of the fluid in the DCT, producing molecular signals that promote renin secretion by other cells of the juxtaglomerular apparatus. The release of renin is an essential component of the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and volume. In response to lowered blood pressure, the macula densa cells release prostaglandins, which triggers granular juxtaglomerular cells lining the afferent arterioles to release renin into the bloodstream. (The juxtaglomerular cells can also release renin independently of the macula densa, as they are also triggered by baroreceptors lining the arterioles, and release renin if a fall in blood pressure in the arterioles is detected.) Furthermore, activation of the sympathetic nervous system stimulates renin release through activation of beta-1 receptors. In response to decreased renal perfusion, renin catalyses the conversion of angiotensin to angiotensin I. Angiotensin-converting enzyme located in the lung then converts angiotensin I to angiotensin II. In addition to its potent vasoconstrictor effects, angiotensin II stimulates the adrenal cortex to release aldosterone, which increases blood volume (and preload) through sodium retention[3].

Aldosterone is synthesized from cholesterol through a series of intermediary metabolites including progesterone, 11-deoxycorticosterone, and corticosterone in the zona glomerulosa of the adrenal cortex. In addition to stimulus from angiotensin II, aldosterone is released in a direct response to hyperkalemia and to a lesser effect of adrenocorticotrophic hormone (ACTH) from the anterior pituitary gland. Aldosterone acts on mineralocorticoid-responsive tissues of epithelial origin, including renal tubule, colon, sweat glands, and salivary glands.

Alterations in the RAAS system is commonly seen in chronic renal disease and Conn's syndrome.

Drugs which act to inhibit the RAAS, such as benazepril, act primarily act through angiotensin converting enzyme inhibition.


  1. Refsal, KR & Harvey, AM (2010) Primary hyperaldosteronism. In August, JR (Ed): Consultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia. pp:254
  2. Atlas, SA (2007) The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm 13(Sb):S9
  3. Williams, GH (2005) Aldosterone biosynthesis, regulation and classical mechanism of action. Heart Fail Rev 10:7